Diagnosis
This patient presented with recurrent episodes of diffuse small bowel wall thickening and ascites associated with diffuse abdominal pain, nausea, and vomiting. Her symptoms resolved spontaneously, correlating with normalization of bowel wall appearance on imaging studies. Initially, the patient’s symptoms were most concerning for infectious or inflammatory enteritis. Infection became lower on the differential as the patient’s symptoms continued to recur and then resolve spontaneously without antiviral or antibiotic treatment. She also had no fevers, and stools samples were negative for infectious causes of her symptoms.
Inflammatory bowel disease (IBD) was considered, but direct visualization of the small bowel and colonic mucosa was unremarkable. In addition, the sporadic nature of her symptoms did not fit the typical IBD presentation. The patient had no risk factors or history that would suggest ischemic disease, vasculitis, or radiation-induced enteritis. Hereditary angioedema and acquired C1 esterase deficiency were considered given the intermittent nature and characteristic quality of her symptoms. However, serum C4 and C1 esterase inhibitor levels returned within normal limits when measured during these episodes. Finally, visceral angioedema was considered.
Visceral angioedema may be related to medications and is specifically associated with angiotensin-converting-enzyme (ACE) inhibitors as well as β-lactams and high doses of nonsteroidal anti-inflammatory drugs (NSAIDs). Given the characteristic presentation with no other inciting cause, the patient’s lisinopril was felt to be the causative agent and was discontinued. Her symptoms resolved completely and never returned. The patient’s final diagnosis was ACE inhibitor-induced visceral angioedema.
About This Condition
Angiotensin-converting enzyme inhibitors were first introduced in the early 1980s and have been prescribed more frequently as the indications for their use have increased. Some estimate that ACE inhibitors are used by more than 40 million people worldwide.1 Angioedema has been reported to occur in 0.1% to 0.2% of patients taking ACE inhibitorsand accounts for 20% to 30% of all angioedema cases presenting to EDs.2,3 However, ACE inhibitors recently have been recognized as a rare cause of angioedema of the gastrointestinal tract. One of the largest literature reviews on ACE inhibitor-induced gastrointestinal angioedema describes only 27 cases.3
Prevalence seems to be highest among middle-aged or older women, particularly among African Americans.3 The interval between medication initiation and onset of symptoms can vary, ranging from 24 hours to 9 years.3,4 In many cases, lack of recognition of this condition early in the disease course led to costly and invasive procedures, such as abdominal laparotomy, before reaching a diagnosis. Other literature reviews report similar patient characteristics and initial disease manifestations: female predominance, often middle-aged, presenting with abdominal pain and emesis associated with bowel wall thickening and ascites on CT.4,5 Additionally, in the majority of cases, visceral angioedema occurred in the absence of oropharyngeal angioedema. Unlike allergic angioedema or NSAID-induced angioedema, ACE inhibitor-induced angioedema is not associated with urticaria.6
The exact pathway of ACE inhibitor-induced angioedema is not completely understood but is thought to be bradykinin mediated. Angiotensin-converting enzyme inhibitors decrease the degradation of bradykinin, which ultimately leads to an increase in vascular permeability and results in an increased plasma extravasation into the interstitial space of subcutaneous or submucosal tissue.1 However, many experts believe that the exclusive role of bradykinin is unlikely. Some suggest that patients with ACE inhibitor-induced angioedema are more likely to have decreased levels or defects in other enzymes such as carboxypeptidase N and aminopeptidase P, which are involved in the breakdown of bradykinin and its metabolites.6 Given the female predominance in this patient population, it also seems reasonable to consider the role of estrogens in the pathogenesis of this disease, although none have been identified to the knowledge of the authors.
Treatment of ACE inhibitor-induced angioedema is largely supportive following discontinuation of the offending medication. There have been case reports of infrequent, mild, recurrent episodes of angioedema, even after ACE inhibitor discontinuation, so these should be anticipated.7
Conclusions
Angiotensin-converting enzyme inhibitor-induced gastrointestinal angioedema is a rare condition. It generally presents as recurrent abdominal pain and nausea with CT findings of intestinal edema and ascites. It is more common among the middle-aged, women, and minorities. ACE inhibitor-induced angioedema should be kept on the differential for patients with the aforementioned characteristics, especially if infection, inflammatory bowel disease, ischemic disease, or vasculitis is deemed unlikely. Identifying this condition early can save patients from unnecessary hospitalizations, physical and emotional discomfort, and further health care costs.